Highly stereoselective synthesis of peracylated α-aldopyranosyl chlorides from aldopyranose peracetates and thionyl chloride catalyzed by BiCl3 generated in situ from the procatalyst BiOCl

Article abstract of DOI:10.1016/j.tetlet.2004.10.138

Aldopyranose peracetates react with thionyl chloride and BiCl₃, generated in situ from a substoichiometric amount of the procatalyst BiOCl, producing the corresponding peracylated aldopyranosyl chlorides in very good to excellent yields (82-97%

Full text of DOI:10.1016/j.tetlet.2004.10.138

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 9631–9634
Highly stereoselective synthesis of peracylated
a-aldopyranosyl chlorides from aldopyranose peracetates and
thionyl chloride catalyzed by BiCl generated in situ
3
from the procatalyst BiOCl
*
Rina Ghosh, Arijit Chakraborty and Swarupananda Maiti
Department of Chemistry, Jadavpur University, Kolkata 700 032, India
Received 23 August 2004; revised 12 October 2004; accepted 22 October 2004
Available online 11 November 2004
Abstract—Aldopyranose peracetates react with thionyl chloride and BiCl , generated in situ from a substoichiometric amount of the
3
procatalyst BiOCl, producing the corresponding peracylated aldopyranosyl chlorides in very good to excellent yields (82–97%) with
exclusive a-anomeric selectivity.
ꢀ
2004 Elsevier Ltd. All rights reserved.
Acylated glycosyl chlorides are important synthetic
1
synthesis of peracylated a-aldopyranosyl chlorides from
aldopyranosyl peracetates and thionyl chloride based on
BiCl generated in situ from a substoichiometric amount
3
a
intermediates for stereoselective glycosylation. They
have been widely employed for the generation of ano-
1
b
1c
1d
meric carbocations, radicals or carbanions. Several
procedures have been developed for the synthesis of b-
glycosyl chlorides but only a few literature reports are
of the procatalyst BiOCl (Schemes 1, 2, and Table 1).
The reported methods show that whereas a protic acid
such as acetic acid or HC1 along with thionyl chloride
2
2
i,l,m
available for the preparation of the corresponding a-
furnishes the b-chloride,
provide exactly the opposite result, producing the
a-anomer.
Lewis acid analogues
3
anomers. Among these, methods utilizing ZnCl –thion-
3
2
b,c
3d
3b,c
yl chloride
and BiCl –trimethylsilyl chloride are
3
worth mentioning. Some of the reported methods have
limitations in terms of yield and selectivity of the prod-
ucts or in respect of the stability, load and cost of the
catalyst. Thus, the search for new methodologies for
their preparation continues.
To establish the minimum procatalyst load and the opti-
mal conditions several experiments were performed.
Under optimized conditions, 1,2,3,4,6-penta-O-acetyl-
D-glucopyranose (1equiv) reacted with thionyl chloride
(2equiv) in the presence of BiOCl (10mol%) in dry
dichloromethane at ambient temperature furnishing
In recent years, Bi(III) salts have been widely used in
4
organic synthesis. BiOCl, although a very mild Lewis
5
acid can generate BiCl in reaction with chlorinating
3
6
agents. Dubac and co-workers first utilized BiOCl as
6
R'
O
OR''
OR''
R'
O
Cl
SOCl (2 eq)/ BiOCl (10-20 mol%)
a procatalyst for Friedel–Crafts acylation reactions.
BiOCl is a moisture stable oxysalt of Bi(III) having very
2
RO
CH Cl /neat, amb. temp.
RO
OR''
4
b
2
2
low toxicity (LD50 ratoral: 22g/kg). In continuation of
our investigations on organic reactions based on BiCl3
generated in situ from the inexpensive procatalyst
OR''
OR''
O
O
AcO
AcO
8
2-97%
7
R = Ac/Bz/
/
BiOCl, we report herein an efficient and stereoselective
AcO
OAc
AcO
OAc
α-only
OAc
OAc
R'= H/Me/CH OAc/CH OBz
2
2
3
Keywords: Stereoselective; Aldopyranosyl chloride; BiCl ; BiOCl; Pro-
R''= Ac/Bz
catalyst; Thionyl chloride.
*
Corresponding author. E-mail: ghoshrina@yahoo.com
Scheme 1.
0
040-4039/$ - see front matter ꢀ 2004Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.10.138

9632
R. Ghosh et al. / Tetrahedron Letters 45 (2004) 9631–9634
BiOCl
SOCl2
SO2
BiCl3
SOCl2
+
O
O
OAc
Cl
OAc
OAc
+
O
BiCl4 + SO2 + AcCl
OAc
OAc
OH
O N
O N
2
2
Scheme 2. Probable mechanistic pathway and catalytic cycle involving the in situ generated BiCl
3
.
Table 1. Synthesis of peracylated a-aldopyranosyl chlorides
a
Entry
Products
Time
% Yield
1
2,3,4,6-Tetra-O-acetyl-a-D-glucopyranosyl chloride
2,3,4,6-Tetra-O-acetyl-a-D-glucopyranosyl chloride
2,3,4,6-Tetra-O-acetyl-a-D-glucopyranosyl chloride
O-acetyl-a-D-glucopyranosyl chloride
Overnight
Overnight
Overnight
Overnight
4.5h
91
91
b
2
c
3
42,3,4
94
88
d
Tetra-
e
5
6
7
8
9
2,3,4,6-Tetra-O-acetyl-a-D-glucopyranosyl chloride
2,3,4,6-Tetra-O-acetyl-a-D-glucopyranosyl chloride
2,3,4,6-Tetra-O-acetyl-a-D-galactopyranosyl chloride
2,3,4,6-Tetra-O-acetyl-a-D-galactopyranosyl chloride
2,3,4,6-Tetra-O-acetyl-a-D-galactopyranosyl chloride
2,3,4,6-Tetra-O-acetyl-a-D-galactopyranosyl chloride
2,3,4,6-Tetra-O-acetyl-a-D-mannopyranosyl chloride
2,3,4-Tri-O-acetyl-a-L-rhamnopyranosyl chloride
2,3,4-Tri-O-acetyl-a-D-arabinopyranosyl chloride
O-acetyl-a-D-xylopyranosyl chloride
97
95
f
Overnight
Overnight
24h
94
94
d
e
2h
96
96
g
10
11
12
13
Overnight
Overnight
1.5h
93
93
82
92
85
Overnight
Overnight
Overnight
Overnight
Overnight
-
Tri-
142,3,4
15
16
17
2,3,4,6-Tetra-O-benzoyl-a-D-glucopyranosyl chloride
Hepta-O-acetyl-a-lactosyl chloride
Hepta-O-acetyl-a-maltosyl chloride
h
83
89
h
a
b
c
3
Isolated pure yield; all products were characterized by IR, NMR and also by comparing the physical data with those of known compounds.
Scale-up (ꢀ20-fold).
With recovered BiOCl.
Without BiOCl.
d
e
In solvent-free conditions.
From 2,3,4,6-tetra-O-acetyl-D-glucopyranose.
From 2,3,4,6-tetra-O-acetyl-D-galactopyranose.
Using 20mol% BiOCl.
f
g
h
exclusively, tetra-O-acetyl-a-D-glucopyranosyl chloride
yields. Reactions of octa-O-acetyllactopyranose (entry
16) and octa-O-acetylmaltopyranose (entry 17) pro-
ceeded smoothly in the presence of BiOCl (20mol%)
leading to the exclusive generation of the desired a-chlo-
rides in very good yields without any cleavage of the
glycosidic bond, which indicates the mildness of the
present procedure compared to some existing
8
,9
in 91% yield (entry 1, Table 1). Similarly, D-galacto-
pyranose pentaacetate (entry 7), D-mannopyranose pen-
taacetate (entry 11) and L-rhamnopyranose tetraacetate
(
entry 12) were converted into the corresponding a-
chloro derivatives overnight in almost quantitative yield.
Pentose sugars such as tetra-O-acetyl-D-arabinopyra-
nose (entry 13) and tetra-O-acetyl-D-xylo- pyranose
2
i,10
methods.
(
in the presence of BiOCl (10mol%) resulting in the
corresponding a-chlorides in very good to excellent
entry 14) also reacted efficiently with thionyl chloride
The reaction was similarly applied to 2,3,4,6-tetra-O-
acetyl-D-glucopyranose (entry 6) and its D-galactose

R. Ghosh et al. / Tetrahedron Letters 45 (2004) 9631–9634
9633
analogue (entry 10). Both of these substrates resulted in
the generation of the corresponding a-glycopyranosyl
chlorides in almost quantitative yields.
as a by-product in this process was also supported by
trapping the same with p-nitrophenol as p-nitrophenyl
acetate (Scheme 2).
2
,3,4,6-Tetra-O-benzoyl-a-D-glucopyranosyl
chloride
It should be mentioned here that while thionyl chloride
alone was found to be capable of transforming penta-O-
acetylgluco- and galactopyranose to the corresponding
tetra-O-acetyl-a-chlorides in excellent yields (entries
4and 8, Table 1), with other peracetylglycopyranoses
of D-xylose, maltose and lactose, reactions were either
sluggish or reluctant to proceed.
was also easily prepared from penta-O-benzoyl-D-gluco-
pyranose in excellent yield and exclusive anomeric selec-
tivity (entry 15, Table 1), thus establishing the
superiority of this procedure compared to that based
on ZnCl -thionyl chloride. Attempted chlorination of
2
glucopyranose pentaacetate with another chlorinating
agent, acetyl chloride and BiCl generated in situ from
3
b
3
3
0mol% of BiOCl, however, did not proceed well.
In summary, we have demonstrated a new, highly effi-
cient stereoselective synthesis of peracylated-a-aldopy-
ranosyl chlorides from aldopyranose peracetates based
on thionyl chloride and the moisture compatible procat-
alyst BiOCl in solvent and solvent-free conditions. The
advantages of the present procedure are: the method is
simple, highly productive and proceeds with exclusive
a-selectivity. BiOCl is an easily available reagent of very
The scope and limitation of this method was further
evaluated by the reaction of penta-O-acetyl-D-gluco-
furanose and 2,3:5,6-diisopropylidene mannose ace-
1
tate with thionyl chloride in the presence of BiOCl
(10mol%), which proceeded at a very slow rate with
b
decomposition and generation of side products.
1
1
2
3
2
,3,4,6-Tetra-O-benzyl-a-D-glucopyranosyl chloride was
low toxicity and can be used to generate BiCl in situ in
3
prepared both from the corresponding hemiacetal and
its 1-O-acetyl derivative at ꢀ10ꢁC, but being unstable,
it could only be isolated in poor yields (30 and 32%).
reaction with thionyl chloride; thus direct handling of
moisture sensitive BiCl can be avoided. Moreover, the
efficient applicability of this methodology in solventless
and in scale-up conditions makes it eco-friendly and it
can thus also be considered for industrial application.
3
To examine further the efficacy of the present procedure
a scale-up experiment (ꢀ20-fold) was performed with
penta-O-acetyl-D-glucopyranose, which proceeded effi-
ciently furnishing the desired product in excellent yield
and with a-selectivity as in the case of entry 1 (entry 2,
Acknowledgements
6
,7
Table 1). BiOCl was recovered and reused in a second
experiment without any loss of activity in terms of yield
and selectivity (entry 3, Table 1). To establish eco-
friendly conditions for these reactions, solventless exam-
ples with gluco and galactopyranose pentaacetates were
performed which proceeded faster than those in solvents
generating the corresponding a-chlorides in almost
quantitative yields (entries 5 and 9, Table 1).
The authors gratefully acknowledge the financial assist-
ance from CSIR, New Delhi (Scheme No. 01/1672/00/
EMR-II) to RG and from UGC, New Delhi to A.C.
(SRF).
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